Choroidal neovascularization (CNV) represents the most common cause of severe vision loss in patients with age-related macular degeneration (AMD). It is also the most common cause of legal blindness in the United States in patients over the age of 60. Therefore, the study of the diagnosis, prevention and treatment of this condition would have a major impact on the public health. We continue to study the pathogenesis and treatment of CNV in an established rodent model of CNV developed in our laboratory. Over the past year, the following has been accomplished: 1. Publication of the finding that bone marrow derived cells incorporate into the CNV and become part of the endothelium - blood vessel structure in mice. In these experiments, transplantation of bone marrow cells from a male C57B16 mouse transgenic for the endothelial specific promoter Tie2 driving the LacZ marker gene was performed into a female nude mouse previously lethally irradiated. By both beta-galactosidase staining and Y-chromosome in-situ, cells derived from the bone marrow transplantation were detected in the CNV within the vascular lumens. 2. Identification of the time course of glial fibrillary acidic protein (GFAP) and vimentin upregulation in eh retina following in the induction and development of CNV in mice. Early results indicate that both of these indicators of retinal injury response appear activated at the very earliest time points of CNV development. These results raise the possibility that concomitant retinal injury overlying an area of CNV may, in part, play a role for vision loss in patients with CNV. 3. Further study of the role of integrin antagonists in CNV. In a laser ? induced animal model of CNV, the use of C16Y, a 12-mer-integrin antagonist with activity against the ?v?3 and ?5?1 integrin units, demonstrated almost complete suppression of the development of CNV. In addition, intravitreal application of this peptide following the appearance of CNV resulted in the regression of the CNV. Both of these results support th importance of integrin expression in the development of CNV. The results further raise the possibility that anti-integrin therapy may be useful modality for both prevention and treatment of active CNV.